The discovery of regulatory non-coding (nc) RNAs has opened a new world in cell biology. Within this class of ncRNAs, microRNAs (miRNAs) have been found to be involved in many cellular functions. Regarding the cardiovascular system, miRNAs regulate cardiomyocyte size and survival, the action potential, angiogenesis, mitochondrial function, and energetics. Moreover, misexpression of miRNAs has been linked to pathology, and altered levels of certain miRNAs even may cause disease. Thus, the manipulation of miRNAs, by affecting the biological processes in which they are implicated, may be used to improve cardiac function. The expression of microRNAs can be modulated through different approaches. This article reviews these issues in relation to the therapeutic potential of miRNAs for heart failure.